Stereoselective Oxidationand Reduction Reactions
Dr Simon WoodwardSchool of Chemistry, University of Nottingham
Oxidation Reactions
• Epoxidation
– Epoxide opening
• Dihydroxylation
• Aminohydroxylation
• Alcohol oxidation
“Click Chemistry: Diverse Chemical Function from a Few Good Reactions” Kolb, Finn, Sharpless, Angew. Chem. Int. Ed. 2001, 40, 2004.
Sharpless Asymmetric Epoxidation of Allylic Alcohols
Review: Katsuki and Martin, Org. React., 1996, 48, 1.
OH
R1R2
R3
(-)-DET "O"
(+)-DET "O"
Sharpless, J. Am. Chem. Soc., 1987, 109, 5765 .Mechanism: J. Am. Chem. Soc., 1991, 113, 106 and 113.
• tBuOOH, Ti(OiPr)4, DET, CH2Cl2, 4Å MS
• Hydroxamic acid ligands for Vanadium-catalysed asymmetric epoxidation of allylic alcohols: Yamamoto, J. Am. Chem. Soc. 2000, 122, 10452.
Chiral Mn(salen) Catalysts: Overview
N N
O OtBu tBu
tButBu
Mn
Cl
H H
Stoichiometric co-oxidants:Usually aq. NaOCl, CH2Cl2mCPBA / NMO (low temperature)
Preparation of catalyst: Organic Syntheses, 1998, 75, 1.Polymer supported catalyst: e.g. Janda, J. Am. Chem. Soc., 2000, 122, 6929.
Cis-Disubstituted alkenes: J. Am. Chem. Soc. 1991, 113, 7063.Trisubstituted alkenes: J. Org. Chem. 1994, 59, 4378.Tetrasubstituted alkenes: Tetrahedron Lett. 1995, 36, 5123.Cinnamate esters: Tetrahedron 1994, 50, 4323.
Review: Katsuki Coord. Chem. Rev. 1995, 140, 189.
• Poor enantioselectivities for trans-disubstituted and terminal alkenes] (but see Katsuki, Synlett, 2000, 1557)
•Via radical intermediate, so stereospecificity with respect to alkene geometry sometimes eroded. Can use to make trans-epoxides from cis-alkenes: Jacobsen, J. Am. Chem. Soc. 1994, 116, 6937.
• Asymmetric epoxidation of E-alkenes using Cr(salens): Gilheany, Org. Lett. 2001, 3, 663, and refs. therein
PhPh
O
0.04eq. (R,R)-Mn(salen)Cl
NaOCl, pH 11.3CH2Cl2, 4ºC
84% yield92% ee
Dioxiranes
R1 R1
O Oxone® (KHSO5)
R1 R2
OO
Base
Isolation of dioxiranes: neutral, anhydrous oxidantsPreparation of dimethyldioxirane (DMDO) solutions: Adam, Chem. Ber., 1991, 124, 2377.More concentrated, “acetone free” solutions: Messeguer, Tetrahedron Lett., 1996, 37, 3585.
• Electrophilic oxidants, but successful for epoxidation of electron poor alkenes: e.g. Baumstark, J. Org. Chem., 1993, 58, 7615.
In situ dioxirane formationBiphasic, CH2Cl2 / H2O: Denmark, J. Org. Chem., 1995, 60, 1391.Monophasic, CH3CN / H2O: Yang, J. Org. Chem., 1995, 60, 3887.In situ DMDO prep.: Shi, J. Org. Chem., 1998, 63, 6425.Trifluoroacetone + H2O2: Shi, J. Org. Chem., 2000, 65, 8808.
Chiral Dioxiranes: Asymmetric Epoxidation of trans-Alkenes
Shi, J. Am. Chem. Soc. 1997, 119, 11224. Review: Shi, Synthesis, 2000, 1979.
• Preparation: 2 steps from D-fructose (enantiomer available in 5 steps from L-sorbose)• Excellent enantioselectivities for epoxidation of trisubstituted and trans-disubstituted alkenes• Poor ee for cis- and terminal alkenes
• Ketone decomposes by Baeyer-Villiger reaction - cannot be recycled. High pH conditions required.
O
O
O
OO
O
PhCH3
30 mol% ketone
Oxone, K2CO3CH3CN, 0ºC
pH 10.5 buffer
PhCH3
O
93% yield; 92% ee
(Use of H2O2 as primary oxidant: Tetrahedron Lett., 1999, 40, 8721;Tetrahedron, 2001, 57, 5213.)
O
OO
OO
OO
RH
R
Other substrate types:Conjugated dienes: J. Org. Chem. 1998, 63, 2948Enynes: Tetrahedron Lett. 1998, 39, 4425.
Modified catalyst for cis-alkenes: J. Am. Chem. Soc. 2000, 122, 11551.Terminal alkenes: Org. Lett., 2001, 3, 1929.
Stable catalysts:Armstrong, Chem. Commun. 1998, 625; Tetrahedron: Asymmetry, 2000, 11, 2057. Shi, Org. Lett. 2001, 3, 715.
Oxidation of silyl enol ethers
Other methods for asymmetric oxidation of silyl enol ethers:Chiral Mn(salens):Thornton, Chem. Commun. 1992, 172; Adam, Tetrahedron Lett. 1996, 37, 6531, and refs. therein.Chiral oxaziridines: Review: Davis, Chem. Rev., 1992, 92, 919.Asymmetric dihydroxylation: J. Org. Chem. 1992, 57, 5067.
Shi, Tetrahedron Lett. 1998, 39, 7819:
Ph
OTBDMS
Ph
OCat. ketone, Oxone
CH3CN, aq. buffer
OH
80% yield90% ee
O OO
O
OO
Ketone =
OR ORO
R=Ac: 59% yield, 74% eeR=Bz: 82% yield, 93% ee
O
OBz
O
OBz
pTsOHsilica gelor YbCl3or AlMe3R=Bz
90% ee 87-91% ee
ShiJ. Am. Chem. Soc. 1999, 121, 4080.
Hydrolytic Kinetic Resolution
Jacobsen, Science 1997, 277, 936. Acc. Chem. Res. 2000, 33, 421.
O1. 0.2 mol% (salen)*Co(III)(OAc) 0.55 eq. H2O, rt, 12 hr
2. Distillation
OOH
OH
> 98% ee(44% yield)
> 98% ee(50% yield)
+
• Catalyst can be recycled (AcOH, air)
• Easily-synthesised oligomeric Co(salen) catalysts are highly active for epoxide opening by water, alcohols and phenols: J. Am. Chem. Soc. 2001, 123, 2687.
Asymmetric Epoxidation of Electron-Deficient Alkenes
R1 R2
O
R1 R2
OO
Review: M.J. Porter and J. Skidmore, Chem. Commun., 2000, 1215.
• Polyleucine, H2O2, base: e.g. Tetrahedron Lett., 2001, 42, 3741. Reviews: Tetrahedron: Asymmetry 1997, 8, 3163; 1998, 9, 1457.
• Catalytic Mg peroxides (tBuOOH, cat. Bu2Mg, cat. diethyl tartrate): R1, R2=Ph Jackson, Angew. Chem., Int. Ed. Engl. 1997, 36, 410. • Chiral phase-transfer catalysts (R2 can be alkyl): Lygo, Tetrahedron, 1999, 55, 6289; Tetrahedron Lett. 2001, 42, 1343.
• Lanthanide catalysis (BINOL, La(OiPr)3 or Yb(OiPr)3, 4Å MS, tBuOOH): R1=Ph, iPr or Me; R2=Ph, iPr, Ph(CH2)2 or Me. La-BINOL-Ph3AsO -mechanistic studies: J. Am. Chem. Soc., 2001, 123, 2725.
• Chiral hydroperoxides, KOH, CH3CN: Adam, J. Am. Chem. Soc., 2000, 122, 5654.
• Stoichiometric zinc alkylperoxides (O2, Et2Zn, R*OH): R1=Ph or tBu, R2=alkyl or aryl Enders, Angew. Chem. Int. Ed. Engl. 1996, 35, 1725; Liebigs Ann. Chem. 1997, 1101
• Chiral dioxiranes: e.g. Tetrahedron: Asymmetry, 2001, 12, 1113.
Alkene Dihydroxylation
R1
R3
R2
R4 R3 R4
OH OHR1 R2
OsO4
R3 R4
O OR1 R2
OsO O
Catalytic systems:• NMO / acetone / H2O (Upjohn procedure): Tetrahedron Lett. 1976, 23, 1973.
• Cat. Me3NO•2H2O, CH2Cl2: Poli, Tetrahedron Lett. 1989, 30, 7385.
• K3Fe(CN)6, K2CO3, tBuOH / H2O: Minato, Yamamoto, Tsuji, J. Org. Chem. 1990, 55, 766.
• NMO, PhB(OH)2, CH2Cl2: Narasaka, Chem. Lett. 1988, 1721. - Diol trapped as boronate ester - useful if diol is unstable or highly water soluble
• Selenoxides as co-oxidants: Krief, Synlett, 2001, 501.
• H2O2, cat. flavin, cat. N-methylmorpholine: Backvall, J. Am. Chem. Soc. 1999, 121, 10424; J. Am. Chem. Soc. 2001, 123, 1365.• H2O2, cat. V(O)(acac)2, NMM, acetone/water: Backvall, Tetrahedron Lett., 2001, 42, 2569.
• O2, K2[OsO2(OH)4], tBuOH / H2O: Beller, Angew. Chem. Int. Ed. 1999, 38, 3026; J. Am. Chem. Soc. 2000, 122, 10289. Wirth, Angew. Chem. Int. Ed. 2000, 39, 334.
Fe-catalysed asymmetric dihydroxylation: Que, J. Am. Chem. Soc. 2001, 123, 6722.
Directed Dihydroxylations
“Kishi rule” - dihydroxylation occurs anti- to oxygen functionality.Review: Cha, Chem. Rev. 1995, 95, 1761.
OH
But
OH
But
OH
But
OsO4, NMO, acetone / H2OOsO4, TMEDA, CH2Cl2, -78ºC
+
OH
OH
OH
OH
anti syn
7:11:24
O
H
But
OsO
N O
O
N
O
OH OH
OsO4, TMEDA
CH2Cl2, -78ºCHO
OH
Regioselectivity > 25:1
Hydroxyl-directed dihydroxylation: Donohoe, Tetrahedron Lett. 1997, 38, 5027.
• Bidentate ligand required
• Dihydroxylation directed by trichloroacetamides: Donohoe, J. Org. Chem. 1999, 64, 2980.• Catalytic directed dihydroxylation of cyclic trichloroacetamides: Donohoe, Tetrahedron Lett. 2000, 41, 4701. • Syn-selective dihydroxylation of acyclic allylic alcohols: Donohoe, Tetrahedron Lett. 1999, 40, 6881.
Sharpless Asymmetric Dihydroxylation
NNO
N
OMe
N
O
N
MeO
H
EtN
Et
H
(DHQD)2-PHAL
AD-Mix:K2OsO2(OH)4, ligand,
K3Fe(CN)6, K2CO3
Review: Sharpless, Chem. Rev. 1994, 94, 2483.
RM
H
RS
RL
"HO" "OH"
"HO" "OH"
-face
-face
slightly hindered
very!!!!!hindered
attractive area - good for aromatic
and alkyl substituents
DHQD= dihydroquinidineDHQ= dihydroquinine "pseudoenantiomers"
DHQ series
DHQD series
Sharpless AD: Recent DevelopmentsImproved ligands:• Pyrimidine (PYR) spacer for sterically congested / terminal alkenes: J.Org. Chem. 1993, 58, 3785.• Anthraquinone (AQN) spacer gives better results for almost all alkenes having only aliphatic substituents: Angew. Chem. Int. Ed. Engl. 1996, 35, 448.
Mechanism:
• Comparison of theoretical and experimental kinetic isotope effects supports [3+2]-mechanism Sharpless, Houk et al. J. Am. Chem. Soc. 1997, 119, 9907.
OOs
O
O O
[3+2]
Os O
OO
OOs O
OO
O[2+2]
OOs
O
O O
Origins of asymmetric induction:Sharpless: J. Am. Chem. Soc. 1997, 119, 1840.Corey (“enzyme like” binding pocket): J. Am. Chem. Soc. 1996, 118, 319; 11038.
Polymer supported chiral ligands: Review: Synlett, 1999, 1181. Crudden, Org. Lett. 2001, 3, 2325. Bolm, Synlett, 2001, 93 (AQN-ligands). Polymer supported Os-catalyst: Kobayashi, J. Am. Chem. Soc. 1999, 121, 11229. Org. Lett. 2001, 3, 2649.
Importance of pH control: improved rates for internal olefins at pH 12 (no MeSO2NH2); higher ee for terminal olefins at pH 10: Beller, Tetrahedron Lett. 2000, 41, 8083.
AminohydroxylationReview: O’Brien, Angew. Chem., Int. Ed. Engl. 1999, 38, 326.
R1
R2
XNClNa (X=Ts, Ms, CBz, Boc, Teoc)OR XNBrLi (X=Ac)
4 mol% K2OsO2(OH)25 mol% (DHQ)2PHAL
1:1 ROH:H2O
R1
R2R1
R2
NHX
OH
OH
NHX
+
• DHQD-ligand series generally provide opposite enantiomer.• Effect of substrate structure on regioselectivity: Janda, Chem. Eur. J. 1999, 5, 1565.
PhCO2Me
PhCO2Me
NHX
OH
X=Ts: 60% yield, 82% eeX=Cbz: 65% yield, 94% ee
Cinnamates:
Styrenes, Aryl alkenes (X=Ts, CBz, Boc, Teoc):
OH
NHBoc
70% yield98% ee
• Altering ligand spacer, solvent can reverse regioselectivity without decreasing ee!
• Aryl esters (and AQN-ligands) give opposite regioselectivity! Panek, Org. Lett. 1999, 1, 1949. • Can be run at higher concentration in presence of acetamide to suppress diol formation: Wuts, Org. Lett. 2000, 2, 2667.
Recent Developments in Asymmetric Aminohydroxylation
• Amino-substituted heterocycles as nitrogen sources: Sharpless, Angew. Chem. Int. Ed. Engl. 1999, 38, 1080.• Adenine derivatives as N-source: Sharpless, Tetrahedron Lett. 1998, 39, 7669.
N N
NH2
1. tBuOCl, EtOH, 0ºC
2. Aq. NaOH, 0ºCN N
N-Cl Na+
PhPh
5% K2OsO2(OH)46% (DHQ)2PHAL
rt
PhPh
OH
NH
N
N
45% yield97% ee
• N-bromo-N-lithio salts of primary carboxamides as N-source: Sharpless, Org. Lett. 2000, 2, 2221.• Unsaturated phosphonates as substrates: Sharpless, J. Org. Chem., 1999, 64, 8379.
Pd-Catalysed Oxidative Kinetic Resolution of Secondary Alcohols with O2
Sigman, J. Am. Chem. Soc. 2001, 123, 7475. Stoltz, J. Am. Chem. Soc. 2001, 123, 7725.
OH O OH5 mol% Pd(nbd)Cl220 mol% (-)-sparteine
3Å MS, 1 atm O2PhCH3, 80ºC
+
(±)
S = kfast/kslow = 47.1
55% conversion5.0 g 2.7 g 2.2 g, 99% ee
NaBH4, MeOH99%
Reduction Reactions
• Hydrogenation
• Transfer hydrogenation
• Boranes
• Hydride reagents
• Hydrosilylation
Asymmetric reduction of alkenes, ketones, imines…….
Monsanto synthesis of L-DOPA
CO2Me
NHAc
CO2Me
NHAc0.1% [(R,R)-(dipamp)Rh(COD)]+BF4
3 atm H2, 50°C, H2O / iPrOH
MeO OMe MeO OMe
CO2-
NH3+
HO OH
HBr
L-DOPA(anti-Parkinson's)
OMe
P P
MeO
Ph
Ph
= (R,R)-dipamp
94% ee
Rh(I)-BINAP Complexes
(S)-BINAP
PPh2
PPh2
[(S)-(BINAP)Rh(nbd)]+ClO4-
Ph NHAc
CO2R
Ph NHAc
CO2R
H2, MeOHR=Me 98%, 93% eeR=H 97%, 100% ee
[(S)-(BINAP)Rh(nbd)]+ClO4-
NHAc
CO2H
Ph NHAc
CO2H
H2, MeOH93%, 87% ee
Ph
Noyori, J. Am. Chem. Soc. 1980, 102, 7932.
Ru BINAP complexes are more general; work for e.g. simple acrylic acids. Mechanistically distinct: Tetrahedron Lett. 1990, 31, 7189.
Rh(I)-diphosphole Complexes
P P
R
RR
R
P
P
R
R
R
RR = Me, Et, Pr
(R,R)-DuPHOS(R,R)-BPE
Review: Burk, Acc. Chem. Res. 2000, 33, 363
0.05% [Rh(R,R-nPr-DuPHOS)(COD)]+TfO-
R2 NHAc
CO2Me
NHAc
CO2Me
2 atm H2, MeOH
R1=H, R2=MeR1=Me, R2=H
R1
99.6% ee99.4% ee
• sense of enantioselectivity independent of acrylamide geometry
Monodentate ligands
O
OPNMe2
O
OP O
(S)-MonoPhos
Ligand A
MonoPhos: deVries, Feringa, J. Am. Chem. Soc. 2000, 122, 11539. Ligand A: Reetz, Angew. Chem. Int. Ed. 2000, 39, 3889.Review: Angew. Chem. Int. Ed. 2001, 40, 1197.
CO2Me
CO2Me
CO2Me
CO2Men% [Rh(cod)2]BF4
2n% ligand, CH2Cl2
(S)-MonophosLigand A
n=5, 1atm H2, 0°Cn=0.1, 1.3 bar H2, rt
94.4% ee99.6% ee
NHAc
CO2Me
NHAc
CO2Men% [Rh(cod)2]BF4
2n% ligand, CH2Cl2
(S)-MonophosLigand A
n=5, 1atm H2, rtn=0.1, 1.3 bar H2, rt
99% ee95.5% ee
Asymmetric Hydrogenation of Functionalised Ketones
OXR
Ru
(S)-BINAP
(R)-BINAP
O
RX
RX
OH
R
MePhMeMe
(CH2)2CH=Me2CH2Cl
Me
X
NMe2NMe2CH2OHCO2MeCO2MeCO2Et
Br
BINAP
969598989897
92
[(Ru(S-BINAP)X2] or [Ru(R,R-iPr-BPE)Br2]
10 atm H2, MeOH
BPE
---
99.3-
76
-
ee
Ru BINAP: J. Am. Chem. Soc. 1987, 109, 5856; J. Am. Chem. Soc. 1988, 110, 629.Ru BPE: J. Am. Chem. Soc. 1995, 115, 4423.
Review: Ager, Tetrahedron Asymm. 1997, 8, 3327.
• Mixed Ru bisphosphine/diamine complexes afford much improved turnover numbers:
0.05% [Ru(R-xylBINAP)Cl2] + R-daipen
1 mol% KOtBu, 8 atm H2, iPrOHPhNMeAc
O
PhNMeAc
OH
87%. 97% ee
PAr2
Ar2P
Ru
Cl
Cl NH2
H2N
OMe
OMe
iPr
• Basic conditions allow dynamic kinetic resolution:
Noyori, J. Am. Chem. Soc. 2000, 122, 6510.
0.33% [Ru(R-xylBINAP)Cl2] + S-daipen
66 mol% KOH, 8 atm H2, iPrOH
98%, 82% ee
O
NHCO2tBu
OH
NHCO2tBu
(±)
Also for reduction of unfunctionalised ketones. Review: Noyori, Angew. Chem., Int. Ed., 2001, 40, 40.
Catalytic asymmetric hydrogenation of aminoketones
Asymmetric Transfer Hydrogenation of KetonesReduction with the aid of a hydrogen donor in the presence of a catalystReviews: Wills, Tetrahedron Asymmetry, 1999, 10, 2045; Noyori, Acc. Chem. Res. 1997, 30, 97.
MO
H
O
L L
R1
R2
Meerwein-Ponndorf-Verley type(main group or lanthanide metals)
(a) (b)
MH O
L LM
H O
L L
O
orM
H O
L L
R1R2
Metal hydride type:transition metals, iPrOH or formate as reductant
0.5% [RuCl2(hexamethylbenzene)2]
Ligand, iPrOH/KOH, 28CR
O
R
OH
X X
NHMe
OH
Ph
Ph
ligand=
XHOMeH
RMeMeEt
Yield947395
% ee927982
Aminoalcohols as ligands:
Arylalkylketones with electron rich aryl groups and benzocycloalkanones suffer from reversibility and give lower ee…but aminoalcohols are generally not compatible with the irreversible hydride donor formic acid
O
RS
NH2
N
Ph
PhRn
SO2Ar
RL
OH
RSRL
O O
MeO
O O
Ru
Cl
O OH
NH2
NH
Ph
Ph
O2S
HN
dend
J. Am. Chem. Soc., 1995, 117, 7562; J. Am. Chem. Soc., 1996, 118, 2521; Chem. Commun., 2001, 1488
iPrOH/KOH or HCO2H/Et3N
0.5%iPrOH/KOH
HCO2H/Et3N97% ee98% ee
72% ee97% ee
97% ee97% ee
91% ee99% ee
- supported and dendritic versions of the ligands have been prepared:
1 % [RuCl2(cymene)]2
1% ligand, HCO2H/Et3N
iPrOH/KOHHCO2H/Et3N
Run:
12345
% ee
96.596.796.796.495.0
conv.
9993868852
ligand:
Monotosylated diamines: formic acid-tolerant ligands for transfer hydrogenation
- monotosylated diamines give slightly less reactive catalysts than the amino alcohols but have proven to be a more useful ligand system for ruthenium based transfer hydrogenations since compatibility with the formic acid system allows efficient reduction even in readily reversible systems:
Ketone Reduction Catalyzed by Oxazaborolidines
N B
O
H PhPh
MeO
RS RS
OH
RL RL+ BH3.THF or catecholborane
(typically ca. 10% loading)
Review: Angew Chem. Int. Ed. 1998, 37, 1986
OH
X
X=HX=MeX=Cl
96.5% ee96.7% ee95.3% ee
tBu
OH
97.3% ee
OH
CO2Me
96.7% eePh
OH
Ph
97% ee
H17C6
OH
95% ee
OH
94% ee
Bu3Sn
TBSO
OH
O O
92% ee
Polymer-supported amino alcohol and in situ generation of borane
Angew. Chem. Int. Ed., 2001, 40,1109
O OH25% catalyst
NaBH4 / TMSCl
THF, reflux
HBr
MeONO2
% ee95.796.184.196.6
Yield98979799
R
R R
SO2
NOH
PhPh
Catalyst:
O
OLiAlH4 Al
H
ORLi+
OAl
O O LiH
R
O
R UnO
AlO O Li
H
R
O
Un R
R1 R2
O
R1 R2
OH
problems: stoichiometric, capricious to prepare, requires long reaction times at very low temperatures
i) (S)-BINOL
ii) ROH
(S)-BINAL-H
Un = aryl, heteroaryl, alkene, alkyne
enantioselectivity is largely electronic in origin:
_
electrostaticrepulsion
Asymmetric reduction of ketones: stoichiometric aluminium hydrides
Noyori, J. Am. Chem. Soc., 1984, 106, 6709, 6717
O
SGa
H
OR'
Li+
Un R
O
O
SGa
O
OR'
Li+ R
Un
H
Un R
OB
Ph
C-EtC
Me
Me
Me
_ _
catecholborane
Un R
Conditions:
2.5 mol% cat.,
-20oC, THF
2-furyl
PhCH=CH-
n-hexyl
Yield ee
95
76
70
60
91
81
75
63
A catalytic binapthyl-substituted hydride source based on hard-soft principles
Woodward, Angew. Chem., Int. Ed. Engl., 1999, 38, 335; Chem. Eur. J. 2000, 6, 3586.
- replacing 'hard' aluminium by 'soft' gallium, the intermediate 'hard' alkoxide can be transferred to the 'hard' borane stoichiometric co-reductant, allowing catalytic turnover:
Ph CH3
O
Ph2PO
Ph2PO OBnO
O
O
Ph CH3
OH
N
N
O
N
O
R R
N
N
O
R
[(pigiphos)Rh(COD)]+ BF4-
87% ee
83% ee1:1:1 (R,R-pybox)/[Rh(COD)Cl]2/AgBF4
or 10:1:1 (S-pymox)/[Rh(COD)Cl]2/AgBF4
Ph2SiH2 or NpPhSiH2
then H3O+ work-up
65% ee
catalyst
(S-pymox)(S,S-pybox)pigiphos
Organometallics, 1991, 10, 560;Tetrahedron:Asymm., 1991, 2, 919
Hydrosilylation of imines/ketones: an alternative to hydrogenative reduction
O OH
NR
HNR
TiF F
TiH
2% cat, 97% ee, 84% yield
0.5% cat, 91% ee, 96% yield
pre-treated catalyst
5 eq. PMHS
THF, 15oC
slow addition of MeOH
5 eq. PMHS, THF, 60oC
slow addition of iBuNH2
pre-treated catalyst
precatalyst =
catalyst =
PhSiH3, piperidine,
MeOH
R = Bn
R = Ph 2% cat, 99% ee, 63% yield
Ph Ph
Asymmetric hydrosilylation of ketones and imines using cheap siloxanes
PMHS = poly(methylhydrosiloxane)
J. Am. Chem. Soc., 1999, 121, 5640 (ketone);Angew. Chem., Int. Ed. Engl., 1998, 37, 1103, Org. Lett., 2000, 2, 713 (imine)
Me3SiO Si OSiMe3
Me
H n
OEt
O
OEt
O
OEtOOEt
O
O
O
OMe
O
O
OMe
(S)-p-Tol-BINAP, CuCl
(S)-p-Tol-BINAP, CuCl
NaOtBu, PMHS, PhCH3
NaOtBu, PMHS, PhCH3
90%85% ee
93%80% ee
(S)-p-Tol-BINAP, CuCl
NaOtBu, PMHS, PhCH3
86%92% ee
Catalytic asymmetric hydrosilylation of enones/enoates
Buchwald, J. Am. Chem. Soc., 1999, 121, 9473; J. Am. Chem. Soc., 2000, 122, 6797
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